azacitidine in treating patients with chronic myelomonocytic leukemia

Conditions: Leukemia

Summary: rationale: drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. purpose: this phase ii trial is studying the side effects of azacitidine and to see how well it works in treating patients with chronic myelomonocytic leukemia.

objectives: primary * to assess the safety and tolerability of azacitidine in patients with chronic myelomonocytic leukemia (cmml). * to assess the overall response rate in these patients. secondary * to assess the incidence of clinical remission/complete remission or partial response in these patients. * to assess hematological improvement in patients treated with this drug. * to assess the overall survival of patients treated with this drug. * to assess progression-free survival of patients treated with this drug. * to assess the time to acute myeloid leukemia (aml) transformation of cmml. * to assess the time to death or aml transformation of cmml. * to assess the biological correlates. outline: this is a multicenter study. patients receive azacitidine subcutaneously on days 1-5 and 8-9. treatment repeats every 4 weeks for at least 6 courses in the absence of loss of response/disease progression or unacceptable toxicity. patients undergo response evaluation after 6 courses or the last course of treatment. responders may continue azacitidine until loss of response/disease progression or unacceptable toxicity. some patients undergo blood, bone marrow, and buccal swab sample collection periodically for correlative studies. after completion of study treatment, patients are followed up for 1 month. peer reviewed and funded or endorsed by cancer research uk

Eligibility criteria:
disease characteristics: * diagnosis of 1 of the following: * all chronic myelomonocytic leukemia (cmml)-2 patients * cmml-1 patients meeting any of the following criteria: * symptomatic bone marrow failure/myeloproliferation defined as any of the following: * red cell transfusion dependence and pre-transfusion hemoglobin \< 9.0 g/dl * symptomatic anemia (hemoglobin \< 11.5 g/dl) * thrombocytopenia (platelet count \< 50 x 10\^9/l) * symptomatic bleeding due to platelet functional defect or disseminated intravascular coagulation (dic)/fibrinolysis * white cell count (wcc) \> 50 x 10\^9/l * düsseldorf score of intermediate or high risk for proliferative cmml-1 (i.e., wcc \> 12 x 10\^9/l) * international prognostic scoring system (ipss) score of intermediate-2 or high risk for non-proliferative cmml-1 (i.e., wcc \< 12 x 10\^9/l) * systemic symptoms including weight loss with no alternative explanation (10% of baseline weight within the past 6 months) * symptomatic splenomegaly * symptomatic extramedullary involvement (e.g. skin infiltration or serous effusions) * no cmml with eosinophilia and 5q33 abnormality patient characteristics: * who performance status 0-2 * creatinine ≤ 2 times upper limit of normal * not pregnant or nursing * negative urine pregnancy test * fertile patients must use at least 2 forms of effective contraception during study and for 3 months after completion of study therapy * no other active malignant disease including basal cell or squamous cell carcinoma of the skin * no known hiv or infectious hepatitis b or hepatitis c * no active infection * no known hypersensitivity to azacitidine or mannitol prior concurrent therapy: * at least 28 days since other prior experimental drug or therapy * no prior chemotherapy for this disease except hydroxycarbamide * no other concurrent anticancer or investigational agents

Keywords: chronic myelomonocytic leukemia